Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
November 1, 2023
Daniel Ryskamp Rijsketic, Austen B Casey, Daniel A N Barbosa et al.
49 citations
Psilocybin increased neural activity (c-Fos expression) in the neocortex, caudoputamen, central amygdala, and parasubthalamic nucleus while decreasing it in the hypothalamus, cortical amygdala, striatum, and pallidum of mice, largely regardless of whether the mice were in their home cage or an enriched environment. Network analyses showed that psilocybin disrupted co-activity between highly correlated brain regions, reduced modularity, and attenuated communication between modules. Context and psilocybin each had widespread effects on brain activity and network architecture, but interactions between the two were surprisingly sparse.
Science advances
April 26, 2024
Ben Rein, Kendall Raymond, Cali Boustani et al.
37 citations
MDMA, a psychoactive drug known for its prosocial effects, enhances empathy-like behaviors in mice by increasing serotonin signaling in the nucleus accumbens. The drug, whether given systemically or infused directly into this brain region, strengthens the social transfer of pain and analgesia, a behavioral test of empathy. Optogenetically stimulating serotonin release in the nucleus accumbens mimics MDMA's effects, confirming serotonin's role. MDMA also restores deficits in empathy-like behaviors in a mouse model of autism lacking the Shank3 gene. The findings indicate that serotonin signaling in the nucleus accumbens is a core mechanism underlying MDMA's empathogenic effects.
bioRxiv (Cold Spring Harbor Laboratory)
April 9, 2025
Odilia D Lu, Katrina White, Kendall Raymond et al.
18 citations
preprint
Psilocybin, the active compound in magic mushrooms, had several clear and repeatable immediate effects on mouse behavior, including increased anxiety and avoidance and reduced fear expression. However, its effects one day later were not consistent across five different laboratories, and no reliable changes were seen in depression-like behavior, fear extinction learning, social preference, or social reward learning. Using about 200 mice per experiment across five independent labs, the findings show that psilocybin's lasting behavioral effects in mice are more modest and less reliable than previously claimed. This coordinated multi-lab approach highlights the importance of replication for producing trustworthy results.
Biological psychiatry
May 5, 2025
Matthew B Pomrenze, Sam Vaillancourt, Pierre Llorach et al.
11 citations
Ketamine produces a rapid increase in movement (locomotor activation) in mice by acting on mu opioid receptors (MORs) in the central amygdala (CeA). This effect is blocked by the opioid receptor antagonist naltrexone, and the same blockade occurs with a MOR-selective antagonist. Whole-brain imaging showed that naltrexone most strongly altered ketamine-induced cFos expression in the CeA, particularly in neurons that co-express MOR and PKCδ. Interrupting MOR function specifically in the CeA, either with a drug or genetic manipulation, prevented ketamine's locomotor effects. This indicates that ketamine's acute behavioral effects involve opioid signaling in the CeA, which may relate to its antidepressant mechanism in humans.
bioRxiv : the preprint server for biology
October 22, 2024
Matthew B Pomrenze, Sam Vaillancourt, Juliana S Salgado et al.
1 citation
preprint
MDMA releases both dopamine and serotonin in the brain's reward center, the nucleus accumbens, but its strong serotonin release limits dopamine release and abuse potential. Using conditional knockout mice and direct brain infusions, the authors show that MDMA's serotonin release, acting through the serotonin transporter and 5-HT2C receptors, reduces the drug's reinforcing effects and conditioned place preference, while its prosocial effects are mediated by separate mechanisms. This platform predicts that (R)-MDMA, a novel entactogen, will have prosocial effects and low abuse potential.
bioRxiv : the preprint server for biology
March 6, 2024
Matthew B Pomrenze, Sam Vaillancourt, Pierre Llorach et al.
1 citation
preprint
Ketamine's effects on movement in mice are blocked by the opioid receptor antagonist naltrexone, but its analgesic and antidepressant-like effects are not. Whole-brain imaging identified the central amygdala as the region most affected by naltrexone, where neurons expressing mu-opioid receptors and PKCδ were strongly activated by naltrexone but not by ketamine. Disrupting mu-opioid receptor function in the central amygdala, either with drugs or genetic techniques, blocked ketamine's locomotor effects. These results indicate that mu-opioid receptors in the central amygdala gate certain behavioral effects of ketamine without being direct targets of the drug.